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Target Concepts:
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Query: EC:4.2.1.22 (
cystathionine beta-synthase
)
965
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hydrogen sulfide (H(2)S) is produced endogenously from l-cysteine in mammalian tissues, and may function as a neuromodulator in the brain as well as a tone regulator in smooth muscle. H(2)S is present at relatively high levels in the brain, and
cystathionine beta-synthase
(
CBS
), which is highly expressed in the hippocampus, is involved in the production of brain H(2)S. Physiological concentrations of H(2)S selectively enhance NMDA receptor-mediated currents and facilitate the induction of hippocampal long-term potentiation (LTP). The NMDA receptor subunits are directly phosphorylated at specific sites by protein kinase A (PKA), resulting in the activation of NMDA-receptor-mediated excitatory postsynaptic currents. PKA activation is also observed in the induction of LTP. Here we show that physiological concentrations of H(2)S increase the production of cAMP in primary cultures of brain cells, neuronal and glial cell lines, and Xenopus oocytes. NMDA receptors expressed on Xenopus oocyte membrane are modulated by H(2)S. This modulation by H(2)S is specifically inhibited by
adenylyl cyclase
-specific inhibitor MDL-12, 330A. The present findings provide a mechanism for the previous observation that H(2)S modulates NMDA receptors and enhances the induction of LTP.
...
PMID:Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor. 1062 86
Current evidence suggests that hydrogen sulfide (H2S) plays an important role in brain functions, probably acting as a neuromodulator as well as an intracellular messenger. In the mammalian CNS, H2S is formed from the amino acid cysteine by the action of
cystathionine beta-synthase
(
CBS
) with serine (Ser) as the by-product. As
CBS
is a calcium and calmodulin dependent enzyme, the biosynthesis of H2S should be acutely controlled by the intracellular concentration of calcium. In addition, it is also regulated by S-adenosylmethionine which acts as an allosteric activator of
CBS
. H2S, as a sulfhydryl compound, has similar reducing properties as glutathione. In neurons, H2S stimulates the production of cAMP probably by direct activation of
adenylyl cyclase
and thus activate cAMP-dependent processes. In astrocytes, H2S increases intracellular calcium to an extent capable of inducing and propagating a "calcium wave", which is a form of calcium signaling among these cells. Possible physiological functions of H2S include potentiating long-term potentials through activation of the NMDA receptors, regulating the redox status, maintaining the excitatory/inhibitory balance in neurotransmission, and inhibiting oxidative damage through scavenging free radicals and reactive species. H2S is also involved in CNS pathologies such as stroke and Alzheimer's disease. In stroke, H2S appears to act as a mediator of ischemic injuries and thus inhibition of its production has been suggested to be a potential treatment approach in stroke therapy.
...
PMID:Hydrogen sulfide: neurochemistry and neurobiology. 1762 56
